Cryptococcus neoformans: A central nervous system isolate from an AIDS patient that is rhinotropic in a normal mouse model

Abstract

A strain of Cryptococcus neoformans that was isolated from the cerebrospinal fluid of a human diagnosed as having acquired immunodeficiency syndrome (AIDS), and that produced cutaneous lesions in experimentally infected, normal mice is described. Although no unusual cutaneous manifestations were noted in the patient's records, this isolate of C. neoformans proved to be dermotropic when injected intravenously into CD-1 mice. The LD50 at 28 days post infection ranged from 3.6-7.5 X 10(5) cells per mouse, and in vitro growth rate studies demonstrated that this isolate grew well at 35 degrees C and at 37 degrees C, but did not grow at 40 degrees C and higher. This isolate was rhinotropic producing large granulomatous lesions in the nasal tissues. Other cutaneous tissues affected were the periocular tissues, ears, feet and tail, although the granulomas were nodular in structure and less necrotic than the nasal lesions. The brain, lungs, liver, kidneys and spleen also were culture positive for C. neoformans. Histopathologically, each affected tissue examined had large densities of yeast cells and a chronic, granulomatous host response. Animals surviving the infection appeared to develop a commensal-type relationship with the infective yeast. This is the first report of an isolate of C. neoformans from an AIDS patient that has caused cutaneous manifestations in an animal model. The model described in this report may be useful for elucidating pathogenic mechanisms of cryptococcosis, particularly cutaneous manifestations of the disease.

Cutaneous cryptococcosis in athymic and beige-athymic mice

“…Dixon and Polak (9) and Fromtling et al (11) described isolates of C. neoformans that were rhinotropic in immunocompetent mice. These isolates also produced cutaneous lesions on the ears, feet, and tail (9,11). Using a guinea pig model, van Cutsem et al (30) were able to establish granulomatous skin ulcerations following i.v.…”

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

“…Although the hematogenous route of CNS entry is well accepted for cryptococcal meningoencephalitis, some strains of C. neoformans isolated from the CSF of human patients were shown to be rhinotropic in mice (398,399), and persistent C. neoformans colonization of the nasal cavity (90 days) was reported in one study (400). These findings prompted investigations into the possibility of an alternative direct route of CNS entry from the nose.…”

Experimental models in antifungal chemotherapy

“…Cyclosporin A, which mainly affects T cells and therefore should worsen the course of Gyptococcus neofomans infection, in fact exerted a genuine chemotherapeutic activity against cryptococcosis [94]. SCID mice are, however, clearly more susceptible to the infection than normal mice [91].…”